Substitution of Brown Norway chromosome 16 preserves cardiac function with aging in a salt-sensitive Dahl consomic rat.
Determination of the genetic factors that control the progression of left ventricular hypertrophy (LVH) to heart failure has been difficult despite extensive study in animal models. Here we have characterized a consomic rat model of LVH resulting from the introgression of chromosome 16 from the normotensive Brown Norway (BN) rat onto the genetic background of the Dahl salt-sensitive (SS/Mcwi) rat by marker assisted breeding. The SS-16BN/Mcwi consomic rats are normotensive but display LVH equivalent to the hypertensive SS/Mcwi rats at early ages. In this study we tracked the development of LVH by echocardiography and analyzed changes in cardiac function and morphology with aging in the SS-16BN/Mcwi, SS/Mcwi, and BN to determine if the consomic SS-16BN/Mcwi was a model of hypertrophic cardiomyopathy (HCM). Aging SS-16BN/Mcwi rats showed no evidence of heart failure or impaired cardiac function upon extensive analysis of left ventricle function by echocardiography and pressure-volume relationships, while their parental SS/Mcwi experienced deterioration in function between 18 and 36 wk of age. In addition aging SS-16BN/Mcwi did not exhibit tissue remodeling common to pathological hypertrophy and HCM such as increased fibrosis and reduced capillary density in the myocardium. In fact, SS-16BN/Mcwi were better protected from developing LV fibrosis with age than either the hypertensive SS/Mcwi or normotensive BN parental strains. This suggests that a gene or genes on chromosome 16 may be involved with both blood pressure regulation and preservation of cardiac function with aging.
Kriegel
A J
AJ
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Greene
A S
AS
D000375:Aging / Q000235:genetics*; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002320:Cardiovascular Physiological Phenomena / Q000235:genetics; D002875:Chromosomes / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl